Novel Cellular and Molecular Mechanisms in Allergic Inflammation

Re^2: Questions (answers?) regarding Schleimer abstract

Robert Schleimer
rschleim@welchlink.welch.jhu.edu

Judah: As usual, you have asked thought-provoking questions. Recently, a major pharma company has analyzed their experience of adverse effects of an ICS which has been administered for tens of millions of person years. The compound was very safe and minimal adverse effects were noted. I think there is at present a bit of an overreaction to the adverse effects of ICS. This results, I believe, in part from the negative advertising approaches that have been used in the competition among ICS manufacturers. Regarding the plateau effect, the beauty of ICS is that they are at the base of the side effect dose response curve while being at the top of the efficacy curve. I am sure that higher doses will bring more side effects. If given in high enough doses, ICS can cause the same side effect profile and severity as oral glucocorticoids. Such doses would be in the many mg range hovever. Regarding differential sensitivity, yes, we find that epithelium>eosinophil>basophil in sensitivity. Several cell types are resistant in vitro, including endothelium, neutrophils, mast cells and B lymphocytes. Thanks for the questions! Bob

Tue Dec 15